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https://www.readbyqxmd.com/read/28922425/hypoxia-inducible-factor-1-alpha-as-a-therapeutic-target-for-primary-effusion-lymphoma
#1
Prabha Shrestha, David A Davis, Ravindra P Veeranna, Robert F Carey, Coralie Viollet, Robert Yarchoan
Primary effusion lymphoma (PEL) is an aggressive B-cell lymphoma with poor prognosis caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Previous studies have revealed that HIF-1α, which mediates much of the cellular response to hypoxia, plays an important role in life cycle of KSHV. KSHV infection promotes HIF-1α activity, and several KSHV genes are in turn activated by HIF-1α. In this study, we investigated the effects of knocking down HIF-1α in PELs. We observed that HIF-1α knockdown in each of two PEL lines leads to a reduction in both aerobic and anaerobic glycolysis as well as lipid biogenesis, indicating that HIF-1α is necessary for maintaining a metabolic state optimal for growth of PEL...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28912871/paeonol-enhances-the-sensitivity-of-human-ovarian-cancer-cells-to-radiotherapy-induced-apoptosis-due-to-downregulation-of-the-phosphatidylinositol-3-kinase-akt-phosphatase-and-tensin-homolog-pathway-and-inhibition-of-vascular-endothelial-growth-factor
#2
Hai-Mei Zhou, Qin-Xiang Sun, Yan Cheng
Radiotherapy is a vital and effective method to treat solid tumors. However, in many tumor types, development of resistance of cancer cells and cytotoxicity in normal tissues presents a major therapeutic problem. It is therefore crucial to identify and develop novel sensitizing agents that may improve the response to radiation therapy without causing any adverse effects. The present study aimed to investigate whether paeonol, a bioactive flavonoid, was able to confer sensitivity to radiation in human ovarian cancer cells...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28842748/pd-l1-expression-correlates-with-vegf-and-microvessel-density-in-patients-with-uniformly-treated-classical-hodgkin-lymphoma
#3
Young Wha Koh, Jae-Ho Han, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh
Recent studies have reported the associations between programmed death-ligand 1 (PD-L1) or PD-L2/PD-1 pathways and pro-angiogenic genes including hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) in several malignancies. However, no study has examined the relationship or prognostic implication of PD-L1, PD-L2, PD-1, VEGF expression, and microvessel density (MVD) in classical Hodgkin lymphoma (cHL) patients. Diagnostic tissues from 109 patients with doxorubicin, bleomycin, vinblastine, and dacarbazine-treated cHL were evaluated retrospectively by immunohistochemical analysis for PD-L1, PD-L2, PD-1, VEGF expression, and for CD31 expression as a measure of MVD...
August 25, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28837676/alk-signaling-cascade-confers-multiple-advantages-to-glioblastoma-cells-through-neovascularization-and-cell-proliferation
#4
Risako Chiba, Masashi Akiya, Miki Hashimura, Yasuko Oguri, Madoka Inukai, Atsuko Hara, Makoto Saegusa
Anaplastic lymphoma kinase (ALK), which is a receptor tyrosine kinase, is essentially and transiently expressed in the developing nervous system. Here we examined the functional role of the ALK gene in glioblastomas (GBMs). In clinical samples of GBMs, high ALK expression without gene rearrangements or mutations was frequently observed in perivascular lesions, in contrast to the relatively low expression in the perinecrotic areas, which was positively correlated with N-myc and phosphorylated (p) Stat3 scores and Ki-67 labeling indices...
2017: PloS One
https://www.readbyqxmd.com/read/28762556/nadph-oxidase-5-nox5-induced-reactive-oxygen-signaling-modulates-normoxic-hif-1%C3%AE-and-p27-kip1-expression-in-malignant-melanoma-and-other-human-tumors
#5
Smitha Antony, Guojian Jiang, Yongzhong Wu, Jennifer L Meitzler, Hala R Makhlouf, Diana C Haines, Donna Butcher, Dave S Hoon, Jiuping Ji, Yiping Zhang, Agnes Juhasz, Jiamo Lu, Han Liu, Iris Dahan, Mariam Konate, Krishnendu K Roy, James H Doroshow
NADPH oxidase 5 (NOX5) generated reactive oxygen species (ROS) have been implicated in signaling cascades that regulate cancer cell proliferation. To evaluate and validate NOX5 expression in human tumors, we screened a broad range of tissue microarrays (TMAs), and report substantial overexpression of NOX5 in malignant melanoma and cancers of the prostate, breast, and ovary. In human UACC-257 melanoma cells that possesses high levels of functional endogenous NOX5, overexpression of NOX5 resulted in enhanced cell growth, increased numbers of BrdU positive cells, and increased γ-H2AX levels...
August 1, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28666189/oral-metronomic-topotecan-sensitizes-crizotinib-antitumor-activity-in-alk-f1174l-drug-resistant-neuroblastoma-preclinical-models
#6
Libo Zhang, Bing Wu, Sylvain Baruchel
BACKGROUND: Anaplastic lymphoma kinase (ALK) inhibitor crizotinib has proven to be effective in the treatment of ALK-mutated neuroblastoma, but crizotinib resistance was commonly observed in patients. We aimed to overcome crizotinib resistance by combining with the MEK inhibitor trametinib or low-dose metronomic (LDM) topotecan in preclinical neuroblastoma models. METHODS: We selected a panel of neuroblastoma cell lines carrying various ALK genetic aberrations to assess the therapeutic efficacy on cell proliferation in vitro...
August 2017: Translational Oncology
https://www.readbyqxmd.com/read/28617871/hypoxia-inducible-factor-1%C3%AE-plays-roles-in-epstein-barr-virus-s-natural-life-cycle-and-tumorigenesis-by-inducing-lytic-infection-through-direct-binding-to-the-immediate-early-bzlf1-gene-promoter
#7
Richard J Kraus, Xianming Yu, Blue-Leaf A Cordes, Saraniya Sathiamoorthi, Tawin Iempridee, Dhananjay M Nawandar, Shidong Ma, James C Romero-Masters, Kyle G McChesney, Zhen Lin, Kathleen R Makielski, Denis L Lee, Paul F Lambert, Eric C Johannsen, Shannon C Kenney, Janet E Mertz
When confronted with poor oxygenation, cells adapt by activating survival signaling pathways, including the oxygen-sensitive transcriptional regulators called hypoxia-inducible factor alphas (HIF-αs). We report here that HIF-1α also regulates the life cycle of Epstein-Barr virus (EBV). Incubation of EBV-positive gastric carcinoma AGS-Akata and SNU-719 and Burkitt lymphoma Sal and KemIII cell lines with a prolyl hydroxylase inhibitor, L-mimosine or deferoxamine, or the NEDDylation inhibitor MLN4924 promoted rapid and sustained accumulation of both HIF-1α and lytic EBV antigens...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28592433/bifurcated-bach2-control-coordinates-mantle-cell-lymphoma-survival-and-dispersal-during-hypoxia
#8
Han Zhang, Zheng Chen, Roberto N Miranda, L Jeffrey Medeiros, Nami McCarty
BACH2, a B-cell-specific transcription factor, plays a critical role in oxidative stress-mediated drug resistance in mantle cell lymphoma (MCL); however, the biological functions of BACH2 and its regulation of B-cell malignancies in chronic hypoxic microenvironment have not been studied. Here, we found that silencing BACH2 led to not only increased tumor formation and colony formation but also increased tumor dispersal to spleen and bone marrow. Decreased BACH2 levels in patients were also correlated with bone marrow and gastrointestinal dispersal of MCL and blastoid subtypes of MCL...
August 10, 2017: Blood
https://www.readbyqxmd.com/read/28586054/propofol-reduces-hypoxia%C3%A2-induced-autophagic-cell-death-through-downregulating-hif-1%C3%AE-in-alveolar-epithelial-type-ii-cells-of-rats
#9
Hui-Jie Ning, Hong-Bin Yuan, Hai-Tao Xu, Xing-Ying He
Propofol (2,6‑diisopropylphenol) exerts protective effects on alveolar epithelial type II (ATII) cells, partly through attenuating hypoxia‑induced apoptosis. Autophagy is involved in the activation of apoptosis. Therefore, the present study investigated the modulating effect of propofol against autophagy in ATII cells under hypoxia. Western blot analysis was performed to detect the protein expression of the autophagy molecular marker, microtubule‑associated protein 1 light chain 3 (LC3)‑II, under various conditions...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28489881/hypoxia-activated-prodrug-th-302-decreased-survival-rate-of-canine-lymphoma-cells-under-hypoxic-condition
#10
Hiroki Yamazaki, Yu-Chang Lai, Morihiro Tateno, Asuka Setoguchi, Yuko Goto-Koshino, Yasuyuki Endo, Munekazu Nakaichi, Hajime Tsujimoto, Naoki Miura
We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells...
2017: PloS One
https://www.readbyqxmd.com/read/28433571/antitumor-and-chemosensitizing-action-of-3-bromopyruvate-implication-of-deregulated-metabolism
#11
Saveg Yadav, Shrish Kumar Pandey, Ajay Kumar, Praveen Kumar Kujur, Rana Pratap Singh, Sukh Mahendra Singh
3-Bromopyruvate (3-BP), brominated derivative of pyruvate, possesses strong antitumor potential, owing to its ability to inhibit multiple target molecules crucial for survival of neoplastic cells. Although, 3-BP displays cytotoxicity against a wide variety of tumors, there is no report with respect to malignancies of thymic origin. Therefore, we investigated its antineoplastic action in vitro against tumor cells of a murine transplantable lymphoma of thymoma origin, designated as Dalton's lymphoma (DL). 3-BP treatment of tumor cells inhibited metabolism and survival with augmented induction of apoptosis and necrosis...
May 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28426671/effect-of-mitochondrially-targeted-carboxy-proxyl-nitroxide-on-akt-mediated-survival-in-daudi-cells-significance-of-a-dual-mode-of-action
#12
Gokul Variar, Tarun Pant, Apoorva Singh, Abinaya Ravichandran, Sushant Swami, Balaraman Kalyanaraman, Anuradha Dhanasekaran
Vicious cycles of mutations and reactive oxygen species (ROS) generation contribute to cancer progression. The use of antioxidants to inhibit ROS generation promotes cytostasis by affecting the mutation cycle and ROS-dependent survival signaling. However, cancer cells select mutations to elevate ROS albeit maintaining mitochondrial hyperpolarization (Δψm), even under hypoxia. From this perspective, the use of drugs that disrupt both ROS generation and Δψm is a viable anticancer strategy. Hence, we studied the effects of mitochondrially targeted carboxy proxyl nitroxide (Mito-CP) and a control ten carbon TPP moiety (Dec-TPP+) in the human Burkitt lymphoma cell line (Daudi) and normal peripheral blood mononuclear cells under hypoxia and normoxia...
2017: PloS One
https://www.readbyqxmd.com/read/28259980/genistein-decreases-a549-cell-viability-via-inhibition-of-the-pi3k-akt-hif%C3%A2-1%C3%AE-vegf-and-nf%C3%A2-%C3%AE%C2%BAb-cox%C3%A2-2-signaling-pathways
#13
Juan Zhang, Hongzheng Su, Qingfeng Li, Jing Li, Qianfeng Zhao
Genistein is an important chemopreventive agent against atherosclerosis and cancer. However, whether genistein is effective in the treatment of lung cancer, and its underlying mechanism, remains to be determined. The present study demonstrated that genistein treatment of A549 lung cancer cells decreased viability in a dose‑ and time‑dependent manner, and induced apoptosis. Additionally, A549 cells exhibited significantly increased reactive oxygen species formation and cytochrome‑c leakage, and activated caspase‑3, B‑cell lymphoma 2‑associated X protein and apoptosis inducing factor expression levels, which are involved in the mitochondrial apoptosis pathway...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28123543/increased-chemosensitivity-and-radiosensitivity-of-human-breast-cancer-cell-lines-treated-with-novel-functionalized-single-walled-carbon-nanotubes
#14
Yijun Jia, Ziyi Weng, Chuanying Wang, Mingjie Zhu, Yunshu Lu, Longlong Ding, Yongkun Wang, Xianhua Cheng, Qing Lin, Kejin Wu
Hypoxia is a major cause of treatment resistance in breast cancer. Single-walled carbon nanotubes (SWCNTs) exhibit unique properties that make them promising candidates for breast cancer treatment. In the present study, a new functionalized single-walled carbon nanotube carrying oxygen was synthesized; it was determined whether this material could increase chemosensitivity and radiosensitivity of human breast cancer cell lines, and the underlying mechanisms were investigated. MDA-MB-231 cells growing in folic acid (FA) free medium, MDA-MB-231 cells growing in medium containing FA and ZR-75-1 cells were treated with chemotherapy drugs or radiotherapy with or without tombarthite-modified-FA-chitosan (R-O2-FA-CHI)-SWCNTs under hypoxic conditions, and the cell viability was determined by water-soluble tetrazolium salts-1 assay...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28104392/scutellarein-antagonizes-the-tumorigenesis-by-modulating-cytokine-vegf-mediated-neoangiogenesis-and-dff-40-actuated-nucleosomal-degradation
#15
Prabhu Thirusangu, V Vigneshwaran, B R Vijay Avin, H Rakesh, H M Vikas, B T Prabhakar
Neoplastic cells often reside in distinctive tumor hypoxia armed with a series of adaptive responses including oxidative stress, defective apoptotic machinery and neoangiogenesis, through that further confer cell survival improvement. Plants still acts as reservoir of natural chemicals to provide newer active pharmacophores. Scutellarein is flavones which has wide range of pharmacophoral effects. In our current research, scutellarein employed for targeting oxidative stress mediated tumor angiogenesis and apoptotic nuclear fragmentation...
February 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27866977/the-anti-hyperplasia-anti-oxidative-and-anti-inflammatory-properties-of-qing-ye-dan-and-swertiamarin-in-testosterone-induced-benign-prostatic-hyperplasia-in-rats
#16
Xinying Wu, Ye Gu, Lun Li
Qing Ye Dan (QYD) is the whole plant of Swertia mileensis and used in Chinese folk medicine for the treatment of prostatitis, benign prostatic hyperplasia (BPH) and so on. This study was to investigate the effects of QYD and its main component swertiamarin on BPH induced by testosterone in rats. The prostatic expressions of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (βFGF) and proliferating cell nuclear antigen (PCNA) were detected by immunohistochemistry assay...
January 4, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/27765090/-effects-of-severe-hypoxia-and-low-concentration-of-serum-protein-on-the-function-of-human-hypertrophic-scar-fibroblasts
#17
J Y Dong, F Song, Y K Liu, X Q Wang
Objective: To simulate the environmental factors during the process of formation and evolution of hypertrophic scar, so as to explore the effects of moderate and severe hypoxia and low concentration of serum protein on the function of human hypertrophic scar fibroblasts (HSFs). Methods: Human HSFs were routinely cultured. Cells of the 3rd to the 6th passage were divided into 10.0% oxygen+ 10.0% fetal calf serum (FCS), 5.0% oxygen+ 5.0% FCS, and 0.5% oxygen+ 0.5% FCS groups according to the random number table...
October 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/27748274/level-of-pax5-in-differential-diagnosis-of-non-hodgkin-s-lymphoma
#18
Brij Bharti, Sachin Shukla, Ratnakar Tripathi, Suman Mishra, Mohan Kumar, Manoj Pandey, Rajnikant Mishra
BACKGROUND & OBJECTIVES: The PAX5, a paired box transcription factor and B-cell activator protein (BSAP), activates B-cell commitment genes and represses non-B-cell lineage genes. About 14 transcript variants of PAX5 have been observed in human. Any alteration in its expression pattern leads to lymphogenesis or associated diseases and carcinogenesis in non-lymphoid tissues. Its mechanisms of function in pathophysiology of non-Hodgkin's lymphoma (NHL) are unclear. This study was intended to explore influence of PAX5 in cascade of NHL pathogenesis and diagnosis...
May 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/27543313/functional-implications-of-the-spectrum-of-bcl2-mutations-in-lymphoma
#19
REVIEW
Khushboo Singh, James M Briggs
Mutations in the translocated BCL2 gene are often detected in diffuse large B-cell lymphomas (DLBCLs), indicating both their significance and pervasiveness. Large series genome sequencing of more than 200 DLBCLs has identified frequent BCL2 mutations clustered in the exons coding for the BH4 domain and the folded loop domain (FLD) of the protein. However, BCL2 mutations are mostly contemplated to represent bystander events with negligible functional impact on the pathogenesis of DLBCL. BCL2 arbitrates apoptosis through a classic interaction between its hydrophobic groove forming BH1-3 domains and the BH3 domain of pro-apoptotic members of the BCL2 family...
July 2016: Mutation Research. Reviews in Mutation Research
https://www.readbyqxmd.com/read/27413173/bortezomib-alleviates-experimental-pulmonary-hypertension-by-regulating-intracellular-calcium-homeostasis-in-pasmcs
#20
Jun Zhang, Wenju Lu, Yuqin Chen, Qian Jiang, Kai Yang, Meichan Li, Ziyi Wang, Xin Duan, Lei Xu, Haiyang Tang, Dejun Sun, Jian Wang
The ubiquitin-proteasome system is considered to be the key regulator of protein degradation. Bortezomib (BTZ) is the first proteasome inhibitor approved by the US Food and Drug Administration for treatment of relapsed multiple myeloma and mantle cell lymphoma. Recently, BTZ treatment was reported to inhibit right ventricular hypertrophy and vascular remodeling in hypoxia-exposed and monocrotaline-injected rats. However, the underlying mechanisms remain poorly understood. We previously confirmed that hypoxia-elevated basal intracellular Ca(2+) concentration ([Ca(2+)]i) and store-operated Ca(2+) entry (SOCE) in pulmonary artery smooth muscle cells (PASMCs) are involved in pulmonary vascular remodeling...
September 1, 2016: American Journal of Physiology. Cell Physiology
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